Our overall objective is to determine the role of endogenously synthesized prostaglandins in controlling the circulation. Toward this goal, we will address five major areas: (1) Renal release of renin, (2) Renal and extrarenal hemodynamic effects of furosemide; (3) Gastric circulation and gastric acid secretion; (4) Uteroplacental circulation and the hemodynamic effects of pregnancy and (5) Role of free radicals in stimulating prostaglandin synthesis. Our approach in vivo will be to use electromagnetic flow probes and radioactive microspheres to measure hemodynamics and gas chromatography-mass spectrometry to measure prostaglandins and metabolites in body fluids. In the kidney we will investigate the role of prostaglandin synthesis in release of renin by adrenergic stimuli. In addition, we will correlate the renal release of renin produced by a prostaglandin dependent stimulus (e.g. activation of the renal baroreceptor) with the renal release of prostaglandin E2, its metabolite 15-keto 13, 14-dihydro PGE2 and 6-keto PGF1 alpha, an index of PGI2 in the blood. We will investigate the requirement for prostaglandins in the extrarenal vascular effects of furosemide. We will investigate the role of prostaglandins in controlling the gastric circulation in vivo and gastric acid secretion in vivo and in isolated parietal cells. The hemodynamic changes occurring in pregnancy will be correlated with postaglandin production. Finally, we will investigate whether free radical producers stimulate prostaglandin synthesis in microsomes and intact cells under hypoxic conditions. This proposal will provide information on the importance of endogenously produced prostaglandins in regulating organ blood flow and function and may give insight into mechanisms whereby certain drugs produce their salutary or adverse effects.